1. Field of the Invention
The present invention relates to a method for improving the rate of successful pancreatic islet transplantation. More particularly, the present invention relates to a method for maintaining high densities of pancreatic islets in culture.
2. Description of the Related Art
The conventional treatment of type I diabetes with intensive insulin regimens using insulin injections or insulin pumps has resulted in limited success in the long-term treatment of diabetics. Pancreatic islet replacement has been promoted as offering a “cure” for diabetes. Successful islet transplantation has been vigorously pursued for its potential in the complete control of glucose (i.e. a system with balanced glucose sensing and insulin secretion).
In the past, most islet transplants failed to achieve long-term insulin independence for the patient. Islet transplants have been faced with problems associated with the isolation and preservation of pancreatic islets. Several studies have reported that graft failure is related to reduced islet viability due to increased apoptosis of the islets stimulated by mechanical and enzymatic damage during the isolation of the islets (Paraskevas, S., et al. Apoptosis occurs in freshly isolated human islets under standard culture conditions, Transplant. Proc. 29:750-752, 1997; Cattan, P., et al. Early assessment of apoptosis in isolated islets of Langerhans. Transplantation 71:857-862, 2001).
In 2001, Gaber et al. showed that culturing islets in a serum-free media for one month allowed the islets to recover from the trauma caused by the isolation process and improved islet graft survival after transplantation (Gaber, et al. Improved in vivo pancreatic islet function after prolonged in vitro islet culture. Transplantation 72:1730-1736, 2001).
In addition, two recent studies (Rutsky, et al. Microgravity culture condition reduces immunogenicity and improves function of pancreatic islets. Transplantation 74:13-21, 2002; Rutsky et al. Microgravity culture conditions decrease immunogenicity but maintain excellent morphology of pancreatic islets. Transplant. Proc. 33:388, 2001) compared mouse islets cultured in a Rotating Cell Culture System (RCCS) manufactured by Synthecon, Inc., Houston, Tex. and in conventional culture dishes. Fresh islets survived less than 15 days when transplanted into streptozotocin diabetic mice; whereas islets cultured in the RCCS or the culture dishes survived for over 100 days after transplantation. Furthermore, only one-third to one-half the number of RCCS-cultured islets were required to maintain euglycemia in the diabetic mice than those cultured in the dishes, indicating that the RCCS-cultured islets either had a better rate of survival or functioned better after being transplanted.
A continuing need exists for improving the culturing of pancreatic islets to enhance the islet viability and improve the survival of transplanted islets.